It is known that 1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-5-isobenzofurance-carbonitrile (INN citalopram) is a well-known antidepressive pharmaceutical active ingredient (DE 2,657,103). The optically active (S)-citalopram having also antidepressive effect is described in EP 346,066.
Several synthetic procedures are known for the preparation of citalopram (WO 98/19512 and WO 98/19513).
It is known from the information leaflet of products containing citalopram—e.g. “Celexa Side Effects Celexa Drug Interactions Citalopram-Rx List Monographs”—that in the course of treatment of depression with citalopram hypotension may occur as an undesirable side effect.
However, this does not mean that citalopram is declared as a product normalizing the blood pressure of patients suffering from hypertension. Firstly: the above mentioned reference does not relate to hypertonic patients. Secondly: it was disclosed that “although the reported cases occurred in the course of treatment carried out with CELEXA™ (citalopram), it is not necessary that said side effect was caused by” CELEXA™ (“CELEXA™” is the trademark of a product containing citalopram). Thirdly: the fact that hypertension, i.e. the opposite to hypotension, was also given as an undesired side effect, strongly supports the statement that the reference contained no unambiguous teaching for hypotension caused by citalopram. Fourthly: the undesired induction of hypotension is not a blood pressure normalizing effect because hypotension is an abnormal blood pressure per Se. For the reasons stated above, the cited reference contains no teaching or disclosure of the use of citalopram for the treatment of hypertension, normalization of blood pressure or decrease of elevated blood pressure respectively.
The aforesaid also relates to the information leaflet of a “SEROPRAM product, active ingredient CITALOPRAM”, wherein the postural type of hypotension was mentioned as undesired side effect.